Many important cell and tissue functions depend on the surface presentation of molecules, so it is critical to determine the chemical state (composition, molecular structure, and orientation) as well as the distribution of biological moieties present on a surface and in the near surface region of biomedical devices. Thus, it is essential to develop surface analysis techniques capable of providing quantitative and detailed surface chemical state information at high spatial resolutions, both for 2-D imaging of surfaces and 3-D imaging of the near surface region. Until recently it was not possible with electron spectroscopy for chemical analysis (ESCA, also known as x-ray photoelectron spectroscopy or XPS) to obtain 3-D images of biological materials by sputter depth profiling. This is because the commercial ion sources available on ESCA instruments produced monoatomic species such as Ar+ that resulted in significant sample degradation and loss of molecular information during sputtering. A few years ago commercial cluster ion sources such C60+ became available on time-of-flight secondary ion mass spectrometry (ToF-SIMS) instruments. These sources were capable of molecular depth profiling of biological materials and opened the possibility of 3-D imaging with ToF-SIMS. Building on the success these cluster ion beam sources have experienced in the ToF-SIMS community, they are now being developed for commercial ESCA instruments. In the Fall of 2008 the manufacturer of our imaging ESCA instrument at the University of Washington (Kratos Analytical) introduced a cluster ion beam source for their AxisUltra DLD instrument, which now makes ESCA molecular depth profiling and 3-D imaging of biological materials possible. To capitalize on these new capabilities and the benefits they will provide to NIH-funded research projects, we are requesting $115,000 to upgrade our existing Kratos Analytical AxisUltra DLD ESCA instrument with the new cluster ion beam source. ESCA and ToF-SIMS are complementary surface analysis techniques. ESCA provides quantitative information about elemental and chemical species composition, while ToF-SIMS provides more detailed molecular structure information. Thus, combined 3-D imaging with both ESCA and ToF-SIMS provide detailed quantitative and molecular structure information about a sample. Research projects that will benefit from the new 3-D ESCA imaging capability include analysis of medical implants (e.g., drug-loaded/coated stents), biofilms, cell sheets, tissue sections, tissue engineering scaffolds, microarray devices (DNA, antibody, carbohydrate, etc.), biosensors, etc. HEALTH RELEVANCE: Knowledge about biomedical implant surfaces and an understanding of how these surfaces interact and direct biological processes when such a device is placed in the body is needed to permit the rational design of new and improved biomedical implants. The proposed cluster ion beam source will provide new information about the surface properties of biomedical devices that is needed to achieve this objective.